Immunotherapies: The New Hope for Cancer Treatment

Despite a steady stream of new, highly-targeted cancer therapies entering the market in recent years, most patients struggling against the disease aren't living much longer. In terms of disease progression and death, health outcomes in oncology really haven't changed that much in 30 years.

Ben Comer

However, the explosion of R&D efforts into immunotherapies—drugs that conspire with the human immune system to curb the haywire replication of cancer cells— represent the next best hope for patients, and for drugmakers hoping to make a splash (and a pile) in oncology.

Jill O'Donnell-Tormey, CEO and director of scientific affairs at the nonprofit Cancer Research Institute (CRI), says immunotherapies, probably in combination, will soon play a major role in the treatment of most cancers. "What has turned the tide for people outside of the hardcore cancer immunologist community is the results we're seeing in areas like non-small cell lung cancer," says O'Donnell-Tormey. "The results in melanoma have been phenomenal, but there's a feeling that melanoma is a particularly immunogenic cancer type. ... I don't think non-small cell lung cancer was ever thought of in that way."

O’Donnell-Tormey

Phase I data combining BMS's Yervoy with an anti-PD1 in melanoma brought the patient response rate up around 50 or 60%, which is promising, and the use of chimeric antigen receptors (CAR) in specific leukemia types like acute lymphoblastic leukemia (ALL) has also generated exciting early-stage data, says O'Donnell-Tormey. Novartis in-licensed a hot rod CAR candidate and "adoptive T cell" therapy from research scientist Carl June and UPenn in 2012.

Big pharma leaders in the programmed cell death (PD-1) and programmed death-ligand (PD-L1) immunotherapy space include BMS, Merck, Roche, and AstraZeneca/MedImmune. AZ fended off a Pfizer acquisition in part due to its belief that Pfizer undervalued its immunotherapy pipeline. Recent estimates by Citibank and Goldman Sachs anticipate the immunotherapy drug market to reach $35 billion and $20 billion a year, respectively, in a decade or sooner.

An important catalyst for early-stage development of new immunotherapy products, especially combinations, is the CRI's Clinical Accelerator program. Shifting from its historical focus on cancer vaccines, the Accelerator program is able to combine unapproved pipeline products—from multiple drug companies—for clinical testing. New combinations are put into clinical trials by CRI with the support of venture funds and philanthropic dollars. CRI partner, the Ludwig Institute, acts as trial sponsor. CRI gets contractual access to experimental candidates, and the owners keep their IP. "The big thing here is that these are not company-sponsored trials," says O'Donnell-Tormey.

The CRI and its clinical trial network come up with an idea and design for a trial, combining whichever drugs it sees fit, regardless of who owns the IP. "We can do some of these combinations before the two companies have to negotiate anything together. ... We're in a neutral space," O'Donnell-Tormey says.

CRI Accelerator trial results are shared, and if two companies decide to develop a combination product further, CRI is eligible for milestones. O'Donnell-Tormey describes the Accelerator as a de-risking option for companies who may not otherwise be able to test combination therapies across organizations with no upfront cost. If the trials fail, no company dollars are lost. The CRI Accelerator's biggest ongoing study at the moment is a combination of AZ/MedImmune's anti-PD-L1 drug MEDI4736 and tremelimumab, the latter (intriguingly, given the acquisition scare) out-licensed from Pfizer to MedImmune in 2011. (AZ completed its acquisition of MedImmune last October.)

June marks the second annual Cancer Immunotherapy Month, as declared by the Cancer Research Institute, and O'Donnell-Tormey says it's terrific to see the CRI's belief and mission validated, after 60 years of dedication to the field. But despite the enormous potential of emerging science and new immunotherapies in cancer, she worries about the research community. "It's a desperate time for scientists," says O'Donnell-Tormey. "NIH is cutting back, and even really senior scientists are saying they can't get grants. I think it will effect young people going into science as well—if there isn't support for them, as much as they love it and are talented in it, if you can't make a career or get your lab funded, it's a problem for science."

Ben Comer is Pharm Exec's Senior Editor. He can be reached at bcomer@advanstar.com.